Role of Noradrenergic and Orexinergic Neurons in General Anesthesia

Kazuyoshi      Hirota; Tetsuya      Kushikata; Mihoko      Kudo

doi:10.2174/1570159033476991

Abstract

Considerable evidence indicates that the GABAA receptor is a molecular target for general anesthetics in the CNS. However, most clinical anesthetists are puzzled by this (unifying) observation as the clinical features of anesthesia differ among anesthetics. Central noradrenergic neurons are known to regulate physiological functions including the sleep-wake cycle, motor activity, and autonomic nervous function. These physiological responses are depressed during general anesthesia. In addition, animal experiments have shown that general anesthetics, which activate GABAA receptors, depress brain noradrenergic neurons. Thus, we have focused on this neuronal system as a “wiring” target for general anesthetic action. However, ketamine, nitrous oxide and xenon, which act as NMDA receptor antagonists, markedly increase noradrenaline release in tissues from several brain regions. Consistent with the clinical features of anesthesia modulation of noradrenergic neurons could differ between the type of anesthetic agents. Therefore, loss of consciousness could be produced by cerebral depression but also over-excitation (e.g. convulsion). Sleep is also induced by not only hypothermia (hibernation) but also body heating that activates heat-sensitive neurons in the preoptic area. Wakefulness, that is to say, may maintain within a set range and that when this range is exceeded (above or below), unconsciousness may be induced. Recently we have accumulated several pieces of evidence supporting this hypothesis. In addition, we found that orexins, wakefulness-promoting neuropeptides, predominantly evoke noradrenaline release from rat cerebrocortical slices, and that activation of orexinergic neurons reduces the duration of anesthesia. Thus, noradrenergic and orexinergic neurons may be involved in the mechanism of general anesthesia.

Keywords: noradrenergic, orexinergic neurons, anesthesia, gabaa receptor, ketamine, nmda receptor antagonists

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